The prostaglandin-stroke program is an interdisciplinary effort to broaden our understanding of the role of Prostaglandins, thromboxane, prostacyclin and leukotrienes in the pathogenesis of thrombotic stroke and to enhance our knowledge concerning the use of eicosanoids and inhibitors in the prevention of stroke. Our major goal is to bring the basic investigations to clinical applications in improved care of patients with stroke and allied disorders. Project 2 aims at determining the role of leukotrines and eicosanoids in cerebral ischemia and stroke and the efficacy of specific inhibitors in intervention of tissue injury in several experimental models. Project 2, 3 and 4 focus on the study of regulation mechanism of eicosanoid synthesis in vascular, blood and brain cells at molecular and cellular levels. Projects 5 and 6 concern platelet and vascular cell arachidonate metabolism and functional changes under controlled shear stress. Project 7 investigates in depth the mechanisms of prostacyclin binding stabilization and transport to platelet PGI2 receptors and the influence of aberration in PGI2 binding ad receptor interaction on thrombotic stroke. Thus, the scope of the program ranges from molecular and cell biology to clinical patient investigations and there exists an exciting potential for a rapid application of basic information to clinical management of stroke and vice versa. The program involves professional personnel with a long record of interests in stroke research who have different but complementary background and expertise in hematology, hemostasis and thrombosis, neurobiology, cell and molecular biology, neurology, biochemistry, pharmacology, tissue culture, enzymology and analytical chemistry. It is intended that this program will enable several laboratories to work individually and together to achieve the highest degree of innovation and production.